This is a proposal to create a Smooth Muscle Plasticity Center of Biomedical Research Excellence (COBRE) at the University of Nevada, Reno (UNR) for the purpose of research in the field of smooth muscle biology and to develop the careers of several highly promising new investigators. The proposed COBRE has a strong thematic focus in the field of smooth muscle biology. Mature smooth muscle cells are unique among muscle cell lineages because they can change phenotype in response to a variety of stimuli. This ability to conform to changing stimuli or microenvironments is referred to as plasticity. Many pathophysiological conditions include or result from phenotypic changes in smooth muscle tissues, but the cause and consequences of remodeling and hypertrophy are not well understood. The COBRE program consists of 5 projects that will investigate various aspects of smooth muscle plasticity. Project 1: Integrins in smooth muscle function to be headed by Dr. Dean Burkin; Project 2: CaM Kinase II in smooth muscle function to be headed by Dr. Brian Perrino; Project 3: will focus on smooth muscle proteomics and will be headed by a new faculty member to be hired by the Biochemistry Department; Project 4: Smooth muscle plasticity during hypertrophy will be headed by Dr. Nick Spencer; Project 5: Stretch-activated K+ channels in regulating smooth muscle contractility will be led by Dr. Sang Don Koh. These projects will be supported by Core facilities, including: Administration and faculty development; Molecular expression and transgenics; Smooth muscle proteomics; and Dynamic imaging. Several new technologies will be provided to the COBRE investigators as a result of these core facilities. The Administrative and faculty development core will support a highly qualified group of faculty mentors, and at least one mentor will be assigned to each of the above project leaders. The mentors will comprise an Internal Faculty Development Committee (IFDC) that will set goals, evaluate progress, and assist the Project Leaders in the central goal of helping them to develop independent funding. To supplement the development of COBRE investigators an extensive faculty development program has been conceived and will be implemented by the IFDC. The COBRE will be led by Drs. Kenton Sanders and Christine Cremo as Principal Investigator and Co-Principal Investigator, respectively. The PI and Co-PI are well qualified, with extensive administrative and scientific experience, to administrate and provide intellectual guidance to this COBRE program. The COBRE program will have strong institutional support from UNR, and will supplement the development of a new biomedical research center at the University, the Nevada Smooth Muscle Research Center.